The overall objective of this project is the application of basic immunochemical techniques to problems of clinical medicine. The specific aims of the project include: further characterization of the pharmacokinetic effects, metabolism and clinical efficacy of Fab fragments of digoxin-specific antibodies; the use of a radioimmunoassay for dihydrodigoxin, an active digoxin metabolite, in studies of the metabolic conversion of digoxin to dihydrodigoxin in man; the experimental characterization of the basis for a clinically important interaction between quinidine and digoxin in man; the application of a propranolol radioimmunoassay to the study of serum concentrations of this beta-adrenergic drug in patients with cardiovascular disease; the continued development of new radioimmunoassay methods for the measurement of serum concentrations of other important molecules in health and various disease states; the use of antibodies specific for fragments of human fibrinogen in characterizing the action of proteolytic enzymes on fibrinogen in various immunological disorders of man; the development of quantitative immunochemical methods for determining the extent of monocyte contamination in supposedly pure human lymphocyte preparations; and, studies of the human cells and cell products involved in the modulation of the immunological response in man.